» Articles » PMID: 19320528

Cytochrome P450 2D6 Genotyping: Potential Role in Improving Treatment Outcomes in Psychiatric Disorders

Overview
Journal CNS Drugs
Specialties Neurology
Pharmacology
Date 2009 Mar 27
PMID 19320528
Citations 8
Authors
Affiliations
Soon will be listed here.
Abstract

The specific reaction toward a given drug varies a lot between individuals and, for many drugs, pharmacogenetic polymorphisms are known to affect biotransformation and clinical outcome. Estimation of the individual's drug-metabolizing capacity can be undertaken by genotyping drug-metabolizing enzymes involved in the respective drug metabolism. Consequences that arise from genotyping may be the adjustment of dose according to genotype, choice of therapeutic strategy, or even choice of drug. One of the first fields where the clinical application of pharmacogenetics may be used is in that of antipsychotic and antidepressant drug treatment because there is a special need for individualized therapy in psychiatry. The pharmacokinetics of many TCAs, some SSRIs and other antidepressant drugs is significantly altered by polymorphisms; however, some controversy still exists as to whether therapeutic efficacy may be improved and/or adverse events can be prevented by genetically driven adjustment of drug dosage. Pharmacogenetic diagnostics may be an important factor in individualizing drug treatment according to the genetic make-up of the patients. However, routine application of pharmacogenetic dose adjustment in clinical practice requires prospective validation.

Citing Articles

CYP2D6 Allelic Variants *34, *17-2, *17-3, and *53 and a Thr309Ala Mutant Display Altered Kinetics and NADPH Coupling in Metabolism of Bufuralol and Dextromethorphan and Altered Susceptibility to Inactivation by SCH 66712.

Glass S, Martell C, Oswalt A, Osorio-Vasquez V, Cho C, Hicks M Drug Metab Dispos. 2018; 46(8):1106-1117.

PMID: 29784728 PMC: 6038030. DOI: 10.1124/dmd.117.079871.


Response to CYP2D6 substrate antidepressants is predicted by a CYP2D6 composite phenotype based on genotype and comedications with CYP2D6 inhibitors.

Gressier F, Verstuyft C, Hardy P, Becquemont L, Corruble E J Neural Transm (Vienna). 2014; 122(1):35-42.

PMID: 25047911 DOI: 10.1007/s00702-014-1273-4.


Pharmacogenomic testing for neuropsychiatric drugs: current status of drug labeling, guidelines for using genetic information, and test options.

Drozda K, Muller D, Bishop J Pharmacotherapy. 2014; 34(2):166-84.

PMID: 24523097 PMC: 3939793. DOI: 10.1002/phar.1398.


Length of psychiatric hospitalization is correlated with CYP2D6 functional status in inpatients with major depressive disorder.

Ruano G, Szarek B, Villagra D, Gorowski K, Kocherla M, Seip R Biomark Med. 2013; 7(3):429-39.

PMID: 23734807 PMC: 4912222. DOI: 10.2217/bmm.13.16.


Importance of pharmacogenetics in the treatment of children with attention deficit hyperactive disorder: a case report.

Tan-Kam T, Suthisisang C, Pavasuthipaisit C, Limsila P, Puangpetch A, Sukasem C Pharmgenomics Pers Med. 2013; 6:3-7.

PMID: 23526481 PMC: 3596139. DOI: 10.2147/PGPM.S36782.


References
1.
Grasmader K, Verwohlt P, Rietschel M, Dragicevic A, Muller M, Hiemke C . Impact of polymorphisms of cytochrome-P450 isoenzymes 2C9, 2C19 and 2D6 on plasma concentrations and clinical effects of antidepressants in a naturalistic clinical setting. Eur J Clin Pharmacol. 2004; 60(5):329-36. DOI: 10.1007/s00228-004-0766-8. View

2.
Otton S, Ball S, Cheung S, Inaba T, Rudolph R, Sellers E . Venlafaxine oxidation in vitro is catalysed by CYP2D6. Br J Clin Pharmacol. 1996; 41(2):149-56. DOI: 10.1111/j.1365-2125.1996.tb00173.x. View

3.
Kirchheiner J, Nickchen K, Bauer M, Wong M, Licinio J, Roots I . Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry. 2004; 9(5):442-73. DOI: 10.1038/sj.mp.4001494. View

4.
Spigset O, Granberg K, Hagg S, Norstrom A, Dahlqvist R . Relationship between fluvoxamine pharmacokinetics and CYP2D6/CYP2C19 phenotype polymorphisms. Eur J Clin Pharmacol. 1997; 52(2):129-33. DOI: 10.1007/s002280050261. View

5.
Thakur M, Grossman I, McCrory D, Orlando L, Steffens D, Cline K . Review of evidence for genetic testing for CYP450 polymorphisms in management of patients with nonpsychotic depression with selective serotonin reuptake inhibitors. Genet Med. 2007; 9(12):826-35. DOI: 10.1097/gim.0b013e31815bf98f. View